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The immense scope for variation in dendritic molecules and their versatile functionalization, with
[...] Read more.The immense scope for variation in dendritic molecules and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. This work shows the advantages of dendronization processes by presenting the synthesis and characterization of different dendronized systems. We were able to achieve final properties with specific potential applications by using different synthetic methodologies for the dendronization process, allowing optimal spatial arrangements of the dendron. View this paper.

The organic chemistry of ruthenium has been one of the most vigorously growing research areas over the past decades. Considerable effort has been extended towards the design and application of a broad series of ruthenium complexes, which culminated with the development by Ryoji

The organic chemistry of ruthenium has been one of the most vigorously growing research areas over the past decades. Considerable effort has been extended towards the design and application of a broad series of ruthenium complexes, which culminated with the development by Ryoji Noyori (2001 Nobel Prize for Chemistry) of chiral ruthenium catalysts for stereoselective hydrogenation reactions [1], and the discovery by Robert H. Grubbs (2005 Nobel Prize for Chemistry) of well-defined ruthenium– benzylidene catalysts for olefin metathesis [2] [...]
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The family of ribosome-inactivating proteins (RIPs) groups all enzymes (EC.3.2.2.22) with a so-called RIP domain which comprises N-glycosidase activity and enables these proteins to catalytically inactivate ribosomes.[...]
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In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide-b-N-isopropylacrylamide) (PDMA-b-PNIPAM) that performed a dual function as both a

In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide-b-N-isopropylacrylamide) (PDMA-b-PNIPAM) that performed a dual function as both a nanoreactor and macro-RAFT agent. The cross-linked polymer particles proved to be in a spherical-like structure of about 50 nm in diameter and with a relatively narrow particle size distribution. 1H-NMR and 19F-NMR spectra showed that thermo-responsive diblock P(DMA-b-NIPAM) and cross-linked PTFEMA particles were successfully synthesized. Influence of the amount of ammonium persulfate (APS), the molar ratio of monomers to RAFT agent, influence of the amount of cross-linker on aqueous polymerization and thermo-responsive characterization of the particles are investigated. Monomer conversion increased from 44% to 94% with increasing the molar ratio of APS and P(DMA-b-NIPAM) from 1:9 to1:3. As the reaction proceeded, the particle size increased from 29 to 49 nm due to the consumption of TFEMA monomer. The size of cross-linked nanoparticles sharply decreased from 50.3 to 40.5 nm over the temperature range 14–44 °C, suggesting good temperature sensitivity for these nanoparticles.
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N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) was synthesized by condensation reaction of 4-chlorobenzenesulphonyl chloride and 2-aminobenzothiazole in acetone under reflux. Neodymium(III) and thallium(III) complexes of the ligand were also synthesized. Both ligand and metal complexes were characterized using UV-Vis, IR, 1H- and 13C-NMR spectroscopies,

N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) was synthesized by condensation reaction of 4-chlorobenzenesulphonyl chloride and 2-aminobenzothiazole in acetone under reflux. Neodymium(III) and thallium(III) complexes of the ligand were also synthesized. Both ligand and metal complexes were characterized using UV-Vis, IR, 1H- and 13C-NMR spectroscopies, elemental analysis and molar conductance measurement. IR studies revealed that the ligand is tridentate and coordinates to the metal ions through nitrogen and oxygen atoms of the sulphonamide group and nitrogen atom attached to benzothiazole ring. The neodymium(III) complex displays a coordination number of eight while thallium(III) complex displays a coordination number of six. The ligand and its complexes were screened in vitro for their antibacterial activities against Escherichia coli strains (E. coli 6 and E. coli 13), Proteus species, Staphylococcus aureus and Pseudomonas aeruginosa using the agar well diffusion technique. The synthesized compounds were found to be more active against the microorganisms screened relative to ciprofloxacin, gentamicin and co-trimoxazole.
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Some novel fluorinated quinazolines (5a–j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, 1H nuclear magnetic

Some novel fluorinated quinazolines (5a–j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, 1H nuclear magnetic resonance (NMR), 13C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.
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The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a–2i and 4a–4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities.
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Wine chemical analysis was carried out on 194 commercial blended red wines produced by two major wine-growing areas—the Aquitaine (France) and Rioja (Spain) regions—in order to compare the wines of both regions. Anthocyanins and derived pigments, tannins and derivatives were identified and quantified

Wine chemical analysis was carried out on 194 commercial blended red wines produced by two major wine-growing areas—the Aquitaine (France) and Rioja (Spain) regions—in order to compare the wines of both regions. Anthocyanins and derived pigments, tannins and derivatives were identified and quantified by HPLC-DAD-ESI-MS/MS (high pressure liquid chromatography coupled to diode array detector and mass spectrometry using the electrospray ionization interface). Mean degree of polymerization (mDP) was determined. The influence of the wine-growing region and the predominance of the properties of some grape varieties used are confirmed by the significant differences observed between both regions. Rioja and Bordeaux “generic” (Bordeaux and Bordeaux-Supérieur appellations) red wines showed the highest anthocyanic content and the highest mDP, as these wines are in a majority made from Merlot (Bordeaux “generic”) and Tempranillo (Rioja). On the contrary, Bordeaux “specific” regions (Blayais, Médoc, Graves, and Libournais) showed the red wines with the highest total phenolic content and tannin concentration, as the predominant grape variety used is Cabernet Sauvignon. A principal component analysis (PCA) and a hierarchical ascendant classification (HAC) suggesting patterns between the chemical parameters and the distribution of the red wines in three groups were proposed. The comparison of the two wine-growing areas also reveals some similarities between the various grape varieties used. A general effect of a progressive decrease in anthocyanins, anthocyanin-derived pigment and tannins is observed for older wines.
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A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was

A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against Fusarium oxysporum f. sp. cucumerinum, Physalospora piricola, Alternaria solani, Cercospora arachidicola, and Gibberella zeae at 50 µg/mL. Compounds 6c (R = i-Pr), 6l (R = o-NO2 Bn), and 6a (R = Et) exhibited excellent antifungal activity against P. piricola with inhibition rates of 98.2%, 96.4%, and 90.7%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide azoxystrobin with a 96.0% inhibition rate, which served as a positive control.
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Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin

Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin cancer remains poorly understood. Here, we have shown that arsenic induces p62 expression in an autophagy-independent manner in human HaCaT keratinocytes. In mouse skin, chronic arsenic exposure through drinking water increases p62 protein levels in the epidermis. Nrf2 is required for basal and arsenic-induced p62 up-regulation. p62 knockdown reduces arsenic-induced Nrf2 activity, and induces sustained p21 up-regulation. p62 induction is associated with increased proliferation in mouse epidermis. p62 knockdown had little effect on arsenic-induced apoptosis, while it decreased cell proliferation following arsenic treatment. Our findings indicate that arsenic induces p62 expression to regulate the Nrf2 pathway in human keratinocytes and suggest that targeting p62 may help prevent arsenic-induced skin cancer.
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The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1–LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty

Cistanoside A (Cis A), an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized

Cistanoside A (Cis A), an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized (OVX) mice model and investigated its underlying molecular mechanisms of action. After 12 weeks of orally-administrated intervention, Cis A (20, 40 and 80 mg/kg body weight/day) exhibited significant antiosteoporotic effects on OVX mice, evidenced by enhanced bone strength, bone mineral density and improved trabecular bone microarchitecture. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline (DPD) and cathepsin K, were decreased, and the bioactivity of bone formation marker alkaline phosphatase (ALP) was increased. Mechanistically, Cis A inhibited the expression of TNF-receptor associated factor 6 (TRAF6), an upstream molecule that is shared by both nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways and subsequently suppressed the levels of receptor activators of nuclear factor kappaB ligand (RANKL), downregulated the expression of NF-κB and upregulated osteoprotegerin (OPG), PI3K and Akt, which means Cis A possessed antiosteoporotic activity in ovariectomized mice via TRAF6-mediated NF-kappaB inactivation and PI3K/Akt activation. Put together, we present novel findings that Cis A, by downregulating TRAF6, coordinates the inhibition of NF-κB and stimulation of PI3K/Akt pathways to promote bone formation and prevent bone resorption. These data demonstrated the potential of Cis A as a promising agent for the treatment of osteoporosis disease.
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P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild to moderate inhibition of P-gp function. Here we report the preparation of a set of substituted 2,3-dioxolane derivatives of poststerone, a known in vivo metabolite of 20-hydroxyecdysone (20E). In contrast with previously studied ecdysteroid dioxolanes, the majority of the new compounds did not inhibit the efflux function of P-gp. Nevertheless, a strong, dose dependent sensitization to doxorubicin was observed on a P-gp transfected cancer cell line and on its susceptible counterpart. We also observed that the MDR cell line was more sensitive to the compounds’ effect than the non-MDR. Our results showed for the first time that the chemo-sensitizing activity of ecdysteroids can be fully independent of functional efflux pump inhibition, and suggest these compounds as favorable leads against MDR cancer.
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Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions

Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature. We computed DFT reactivity indices at the B3LYP/6-311G(2d,p)//B3LYP/6-31G(d,p) and employed the grand potential stabilization criterion to calculate the preferred regioisomer. Experimental and calculated regioselectivity agree in the vast majority of cases. It was concluded that predominance of a single regioisomer can be obtained by maximizing (i) the chemical potential difference between nitrilimine and alkene and (ii) the local softness difference between the reactive atomic sites within each reactant. Such maximization can be achieved by carefully selecting the substituents on both reactants.
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A comprehensive study on essential oils extracted from different Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball samples from Tarquinia (Italy) is reported. In this study, the 24-h steam distillation procedure for essential oil preparation, in terms of different harvesting and extraction times,

A comprehensive study on essential oils extracted from different Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball samples from Tarquinia (Italy) is reported. In this study, the 24-h steam distillation procedure for essential oil preparation, in terms of different harvesting and extraction times, was applied. The Gas chromatography–mass spectrometry (GC/MS) analysis showed that C. nepeta (L.) Savi subsp. glandulosa (Req.) Ball essential oils from Tarquinia belong to the pulegone-rich chemotype. The analysis of 44 samples revealed that along with pulegone, some other chemicals may participate in exerting the related antifungal activity. The results indicated that for higher activity, the essential oils should be produced with at least a 6-h steam distillation process. Even though it is not so dependent on the period of harvesting, it could be recommended not to harvest the plant in the fruiting stage, since no significant antifungal effect was shown. The maximum essential oil yield was obtained in August, with the highest pulegone percentage. To obtain the oil with a higher content of menthone, September and October should be considered as the optimal periods. Regarding the extraction duration, vegetative stage material gives the oil in the first 3 h, while material from the reproductive phase should be extracted at least at 6 or even 12 h.
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Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects

Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function),and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy.
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The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography‐mass spectrometry (GC‐MS) analysis. GC‐MS analyses revealed the presence of 31 components, with 5‐(3‐buten‐1‐yn‐1‐yl)‐2,2′‐bithiophene (5‐BBT, 27.63%), αterthienyl (α‐T, 14.95%),1,8‐cineole (5.56%) and cis‐β‐ocimene (5.01%) being the four major constituents. Based bioactivity‐directed chromatographic separation of the essential oil led to the isolation of 5‐BBT, 5‐(4‐isovaleroyloxybut‐1‐ynyl)‐2,2′‐bithiophene (5‐IBT) and αT as active compounds. The essential oil of E. grijsii exhibited larvicidal activity against the fourth instar larvae of Aedes albopictus, Anopheles sinensis and Culex pipiens pallens with LC50 values of 2.65 μg/mL, 3.43 μg/mL and 1.47 μg/mL, respectively. The isolated thiophenes, 5‐BBT and 5‐IBT, possessed strong larvicidal activity against the fourth instar larvae of Ae. albopictus(LC50 = 0.34 μg/mL and 0.45 μg/mL, respectively) and An. sinensis(LC50 = 1.36 μg/mL and 5.36 μg/mL, respectively). The two isolated thiophenes also had LC50 values against the fourth instar larvae of C. pipiens pallens of 0.12 μg/mL and 0.33 μg/mL, respectively. The findings indicated that the essential oil of E. grijsii roots and the isolated thiophenes have an excellent potential for use in the control of Ae.albopictus, An. sinensis and C. pipiens pallens larvae and could be used in the search for new, safer and more effective natural compounds as larvicides.
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Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala‐aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The

Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala‐aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The Morita‐Baylis‐Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis. We present here the design, synthesis and in vitro screening against Leishmania donovani of sixteen new molecular hybrids from analgesic/antiinflammatory tetrahydropyrans derivatives and Morita˗Baylis˗Hillman adducts. First, acrylates were synthesized from analgesic/anti‐inflammatory tetrahydropyrans using acrylic acid under TsOH as a catalyst (70–75% yields). After the 16 new MBHAs were prepared in moderate to good yields (60–95%) promoted by microwave irradiation or low temperature (0 °C) in protic and aprotic medium. The hybrids were evaluated in vitro on the promastigote stage of Leishmania donovani by determining their inhibitory concentrations 50% (IC50), 50% hemolysis concentration (HC50), selectivity index (HC50/IC50,), and comparing to Amphotericin B, chosen as the anti‐leishmanial reference drug. The hybrid which presents the bromine atom in its chemical structure presents high leishmanicide activity and the high selectivity index in red blood cells (SIrb > 180.19), compared with the highly‐toxic reference drug (SIrb = 33.05), indicating that the bromine hybrid is a promising compound for further biological studies.
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Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we

Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we hypothesized that human quinone reductase 2 (hQR2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives. Therefore, we investigated the role of hQR2 in the reduction of indolone derivatives. We analyzed the interaction between hQR2 and several indolone-type derivatives by examining enzymatic kinetics, the substrate/protein complex structure with X-ray diffraction analysis, and the production of free radicals with electron paramagnetic resonance. The reduction of each compound in cells overexpressing hQR2 was compared to its reduction in naïve cells. This process could be inhibited by the specific hQR2 inhibitor, S29434. These results confirmed that the anti-malarial activity of indolone-type derivatives was linked to their ability to serve as hQR2 substrates and not as hQR2 inhibitors as reported for chloroquine, leading to the possibility that substrate of hQR2 could be considered as a new avenue for the design of new antimalarial compounds.
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The structure of fuliginone was revised from a phenyl substituted phenalenone to a hydroxyl substituted phenalenone as a result of its re‐purification via HPLC with subsequent NMR analysis together with an independent synthesis and analysis of the crystal structure, which was secured via

The structure of fuliginone was revised from a phenyl substituted phenalenone to a hydroxyl substituted phenalenone as a result of its re‐purification via HPLC with subsequent NMR analysis together with an independent synthesis and analysis of the crystal structure, which was secured via the crystalline sponge method. On‐flow High Performance Liquid Chromatography coupled to Nuclear Magnetic Resonance spectroscopy (HPLC‐NMR) was employed to confirm the presence of the natural product in the plant extract and to monitor for any possible degradation or conversion of the compound.
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Lipases from Thermomyces lanuginosus (TLL) and Pseudomonas fluorescens (PFL) wereimmobilized on functionalized silica particles aiming their use in the synthesis of fructose oleate in a tert‐butyl alcohol/water system. Silica particles were chemically modified with octyl (OS), octyl plus glutaraldehyde (OSGlu), octyl plus glyoxyl(OSGlx), and octyl plus epoxy groups(OSEpx). PFL was hyperactivated on all functionalized supports (more than 100% recovered activity) using low protein loading (1 mg/g), however, for TLL, this phenomenon was observed only using octyl‐silica (OS). All prepared biocatalysts exhibited high stability by incubating in tert‐butyl alcohol (half‐lives around 50 h at 65 °C). The biocatalysts prepared using OS and OSGlu as supports showed excellent performance in the synthesis of fructose oleate. High estersynthesis was observed when a small amount of water (1%, v/v) was added to the organic phase, allowing an ester productivity until five times (0.88–0.96 g/L.h) higher than in the absence of water (0.18–0.34 g/L.h) under fixed enzyme concentration (0.51 IU/g of solvent). Maximum ester productivity (16.1–18.1 g/L.h) was achieved for 30 min of reaction catalyzed by immobilized lipases on OS and OSGlu at 8.4 IU/mL of solvent. Operational stability tests showed satisfactory stability after four consecutive cycles of reaction.
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A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide‐binding domain leucine‐rich repeat containing protein family，pyrin domain‐containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ‐09 and TBZ‐21, were identified by

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide‐binding domain leucine‐rich repeat containing protein family，pyrin domain‐containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ‐09 and TBZ‐21, were identified by antiproduction of IL‐1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti‐inflammatory activities were investigated. Several compounds were identified as anti‐inflammatory agents that can reduce IL‐1β expression in a dosedependent manner. A preliminary structure–activity relationship is also summarized here.
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Zuojin formula (ZJ) is a traditional Chinese medicine (TCM) prescription consisted of Coptidis Rhizoma (CR) and Euodiae Fructus (EF), and has been used to treat gastrointestinal (GI) disease for more than 700 years. Fan-Zuojin formula (FZJ) is a related TCM prescription also consisted

Zuojin formula (ZJ) is a traditional Chinese medicine (TCM) prescription consisted of Coptidis Rhizoma (CR) and Euodiae Fructus (EF), and has been used to treat gastrointestinal (GI) disease for more than 700 years. Fan-Zuojin formula (FZJ) is a related TCM prescription also consisted of CR and EF with the opposite proportion. In recent years, ZJ was getting more attention for its antitumor potential, but the indeterminate pharmacokinetic (PK) behavior restricted its clinical applications, and the PK differences between ZJ and FZJ were also largely unknown. Consequently it is necessary to carry out a full-scale PK study to demonstrate the physiological disposition of ZJ, as well as the comparative PK study between ZJ and FZJ to illustrate the compatibility dose effects. Therefore a liquid chromatographic–tandem mass spectrometry (LC–MS/MS) method was established and validated for the determinations of coptisine, epiberberine, palmatine, berberine, 8-oxocoptisine, 8-oxoepiberberine, noroxyhydrastinine, corydaldine, dehydroevodiamine, evodiamine, wuchuyuamide-I, and evocarpine in rat plasma. PK characteristics of 12 alkaloids after oral administration of ZJ and FZJ were compared, and the result was analyzed and discussed with the help of an in silico study. Then an integrated PK study was carried out with the AUC-based weighting method and the total drug concentration method. The established method has been successfully applied to reveal the PK profiles of the 12 alkaloids in rat plasma after oral administration of ZJ and FZJ. The results showed that: (1) double peaks were observed in the plasma concentration-time (C–T) curves of the alkaloids after ZJ administration; but the C–T curves approximately matched the two-compartment model after FZJ administration; (2) There were wide variations in the absorption levels of these alkaloids; and even for a certain alkaloid, the dose modified systemic exposure levels and elimination rate also varied significantly after administration of ZJ and FZJ extracts. The results could be interpreted as follows: firstly, inhibition effect on GI motility caused by the high content CR alkaloids (especially berberine) in ZJ could delay the Tmax, and increase the absorption and systemic exposure levels of the other alkaloids, and also lead to the double peak phenomenon of these alkaloids. However, for quaternary protoberberine alkaloids (QPA), double peaks were primarily caused by the different Ka value in two intestinal absorption sites. Secondly, absorption was the major obstacle to the systemic exposure level of the alkaloids from CR and EF. In silico and PK studies suggested that the absorption of these alkaloids, except QPAs, mainly depended on their solubility rather than permeability. Thirdly, EF could promote the absorption and accelerate the elimination of QPAs, and had a greater influence on the former than the latter. At last the integrated PK analysis suggested that berberine and dehydroevodiamine could be regarded as the representative components to reflect the PK behaviors of CR and EF alkaloids after administration of ZJ and FZJ. In conclusion, the absorption, elimination and systemic exposure level of these alkaloids were mainly influenced by the proportion of EF and CR, the pharmacological effect on GI motility, and the physicochemical property of these alkaloids. These findings would be helpful for a better understanding of the activities and clinical applications of ZJ, FZJ and other related TCM prescriptions.
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Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2–5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.
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The relationship between berry chemical composition, region of origin and quality grade was investigated for Chardonnay grapes sourced from vineyards located in seven South Australian Geographical Indications (GI). Measurements of basic chemical parameters, amino acids, elements, and free and bound volatiles were conducted

The relationship between berry chemical composition, region of origin and quality grade was investigated for Chardonnay grapes sourced from vineyards located in seven South Australian Geographical Indications (GI). Measurements of basic chemical parameters, amino acids, elements, and free and bound volatiles were conducted for grapes collected during 2015 and 2016. Multiple factor analysis (MFA) was used to determine the sets of data that best discriminated each GI and quality grade. Important components for the discrimination of grapes based on GI were 2-phenylethanol, benzyl alcohol and C6 compounds, as well as Cu, Zn, and Mg, titratable acidity (TA), total soluble solids (TSS), and pH. Discriminant analysis (DA) based on MFA results correctly classified 100% of the samples into GI in 2015 and 2016. Classification according to grade was achieved based on the results for elements such as Cu, Na, Fe, volatiles including C6 and aryl alcohols, hydrolytically-released volatiles such as (Z)-linalool oxide and vitispirane, pH, TSS, alanine and proline. Correct classification through DA according to grade was 100% for both vintages. Significant correlations were observed between climate, GI, grade, and berry composition. Climate influenced the synthesis of free and bound volatiles as well as amino acids, sugars, and acids, as a result of higher temperatures and precipitation.
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Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocyte model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 h before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, CD36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results suggest that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.
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Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a

Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.
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In this study, magnetic graphene oxide (MGO) nanomaterials were synthesized based on covalent binding of amino Fe3O4 nanoparticles onto the graphene oxide (GO), and the prepared MGO was successfully applied as support for the immobilization of laccase. The MGO-laccase was characterized by transmission

In this study, magnetic graphene oxide (MGO) nanomaterials were synthesized based on covalent binding of amino Fe3O4 nanoparticles onto the graphene oxide (GO), and the prepared MGO was successfully applied as support for the immobilization of laccase. The MGO-laccase was characterized by transmission electron microscopy (TEM) and a vibrating sample magnetometer (VSM). Compared with free laccase, the MGO-laccase exhibited better pH and thermal stabilities. The optimum pH and temperature were confirmed as pH 3.0 and 35 °C. Moreover, the MGO-laccase exhibited sufficient magnetic response and satisfied reusability after being retained by magnetic separation. The MGO-laccase maintained 59.8% activity after ten uses. MGO-laccase were finally utilized in the decolorization of dye solutions and the decolorization rate of crystal violet (CV), malachite green (MG), and brilliant green (BG) reached 94.7% of CV, 95.6% of MG, and 91.4% of BG respectively. The experimental results indicated the MGO-laccase nanomaterials had a good catalysis ability to decolorize dyes in aqueous solution. Compared with the free enzyme, the employment of MGO as enzyme immobilization support could efficiently enhance the availability and facilitate the application of laccase.
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The chemical composition of the essential oil of the flowering aerial parts of Monarda didyma L. cultivated in central Italy was analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). The major compounds of the oil were thymol (59.3%), p-cymene (10.3%), terpinolene (9.2%), δ-3-carene (4.4%), myrcene

Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37Rv that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42

Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37Rv that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42 μM. The best MIC (6 μM) was displayed by 3-[(4-methylbenzyl)amino]pyrazine-2-carboxamide (8) that also showed low cytotoxicity in the HepG2 cell line (IC50 ≥ 250 μM). Only moderate activity against Enterococcus faecalis and Staphylococcus aureus was observed. No activity was detected against any of tested fungal strains. Molecular docking with mycobacterial enoyl-ACP reductase (InhA) was performed to investigate the possible target of the prepared compounds. Active compounds shared common binding interactions of known InhAinhibitors. Antimycobacterial activity of the title compounds was compared to the previously published benzylamino-substituted pyrazines with differing substitution on the pyrazine core (carbonitrile moiety). The title series possessed comparable activity and lower cytotoxicity than molecules containing a carbonitrile group on the pyrazine ring.
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Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship) study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation) of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship) models were developed, using PLS (partial least squares regression) and MLR (multiple linear regression). On the one hand, these models allow for the indication of the most important descriptors (molecular properties) responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study.
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Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of anumberofdensityfunctionalswhoseaccuracyhasbeentestedacrossabroadspectrumofdatabases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through

Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of anumberofdensityfunctionalswhoseaccuracyhasbeentestedacrossabroadspectrumofdatabases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through Conceptual DFT in an attempt to relate their intrinsic chemical reactivity with the ability to inhibit the action of glycating carbonyl compounds on amino acids and proteins. This knowledge could be useful in the design and development of new drugs which can be potential medicines for diabetes and Alzheimer’s disease.
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A theoretical study of the peri interactions, both intramolecular hydrogen (HB) and chalcogen bonds (YB), in 1-hydroxy-8YH-naphthalene, 1,4-dihydroxy-5,8-di-YH-naphthalene, and 1,5-dihydroxy-4,8-di-YH-naphthalene, with Y = O, S, and Se was carried out. The systems with a OH:Y hydrogen bond are the most stable ones followed

A theoretical study of the peri interactions, both intramolecular hydrogen (HB) and chalcogen bonds (YB), in 1-hydroxy-8YH-naphthalene, 1,4-dihydroxy-5,8-di-YH-naphthalene, and 1,5-dihydroxy-4,8-di-YH-naphthalene, with Y = O, S, and Se was carried out. The systems with a OH:Y hydrogen bond are the most stable ones followed by those with a chalcogen O:Y interaction, those with a YH:O hydrogen bond (Y = S and Se) being the least stable ones. The electron density values at the hydrogen bond critical points indicate that they have partial covalent character. Natural Bond Orbital (NBO) analysis shows stabilization due to the charge transfer between lone pair orbitals towards empty Y-H that correlate with the interatomic distances. The electron density shift maps and non-covalent indexes in the different systems are consistent with the relative strength of the interactions. The structures found on the CSD were used to compare the experimental and calculated results.
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In this study, the subcritical butane extraction process of fenugreek seed oil was optimized using response surface methodology with a Box-Behnken design. The optimum conditions for extracted oil from fenugreek seed was as follows: extraction temperature of 43.24 °C , extraction time of

In this study, the subcritical butane extraction process of fenugreek seed oil was optimized using response surface methodology with a Box-Behnken design. The optimum conditions for extracted oil from fenugreek seed was as follows: extraction temperature of 43.24 °C , extraction time of 32.80 min, and particle size of 0.26 mm. No significant differences were found between the experimental and predicted values. The physical and chemical properties of the oil showed that the oil could be used as edible oil. Fatty acid composition of oils obtained by subcritical butane under the optimum conditions and by accelerated solvent extraction showed negligible difference. The oils were rich in linoleic acid (42.71%–42.80%), linolenic acid (26.03%-26.15%), and oleic acid (14.24%-14.40%). The results revealed that the proposed method was feasible, and this essay shows the way to exploit fenugreek seeds by subcritical butane extraction under the scope of edible oils.
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In this work, the n-butanol extract from leaves of Lonicera japonica Thunb. (L. japonica) was reacted with DPPH and subjected to a HPLC analysis for the guided screening antioxidants (DPPH-HPLC experiments). Then, nine antioxidants, including flavonoid glycosides and caffeoylquinic acid derivatives, were isolated

(1) Background: The great potential of RNA interference (RNAi)-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs) to target tissues and cells. Hence, we aimed at developing and examining a novel integrin αvβ3-specific delivery

(1) Background: The great potential of RNA interference (RNAi)-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs) to target tissues and cells. Hence, we aimed at developing and examining a novel integrin αvβ3-specific delivery carrier for targeted transfection of siRNA to malignant tumor cells; (2) Methods: Arginine-glycine-aspartate motif (RGD) was adopted as a tissue target for specific recognition of integrin αvβ3. To enable siRNA binding, a chimeric peptide was synthesized by adding nonamer arginine residues (9R) at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD)2-9R. The efficiency of 9R peptide transferring siRNA was biologically evaluated in vitro by flow cytometry, confocal microscopy, and Western blot; (3) Results: An optimal 10:1 molar ratio of c(RGD)2-9R to siRNA was confirmed by the electrophoresis on agarose gels. Both the flow cytometry and confocal microscopy results testified that transfection of c(RGD)2-9R as an siRNA delivery carrier was obviously higher than the naked-siRNA group. The results of Western blot demonstrated that these 9R peptides were able to transduce siRNA to HepG2 cells in vitro, resulting in efficient gene silencing; and (4) Conclusion: The chimeric peptide of c(RGD)2-9R can be developed as an effective siRNA delivery carrier and shows potential as a new strategy for RNAi-based gene therapy.
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This study is the first to report the use of response surface methodology to improve phenolic yield and antioxidant activity of Acer truncatum leaves extracts (ATLs) obtained by ultrasonic-assisted extraction. The phenolic composition in ATLs extracted under the optimized conditions were characterized by

This study is the first to report the use of response surface methodology to improve phenolic yield and antioxidant activity of Acer truncatum leaves extracts (ATLs) obtained by ultrasonic-assisted extraction. The phenolic composition in ATLs extracted under the optimized conditions were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X1), material-to-liquid ratio (X2), ultrasonic temperature (X3) and power (X4) for an optimal total phenol yield (Y1) and DPPH• antioxidant activity (Y2). The results showed that the optimal combination was ethanol:water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic bath temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent/100 g d.w. and a maximal DPPH• antioxidant activity of 74,241.61 μmol Trolox equivalent/100 g d.w. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic components in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloylglucoside was proposed. All these results provide practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.
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The preliminary structure, in vitro antioxidant and in vivo hepatoprotective activities of water-soluble polysaccharides (ORWP) and alkali-soluble polysaccharides (ORAP), prepared from the mushroom Oudemansiella radicata, were investigated. Both ORWP and ORAP were heteropolysaccharides with mannose, glucose and galactose being the main monosaccharide

The preliminary structure, in vitro antioxidant and in vivo hepatoprotective activities of water-soluble polysaccharides (ORWP) and alkali-soluble polysaccharides (ORAP), prepared from the mushroom Oudemansiella radicata, were investigated. Both ORWP and ORAP were heteropolysaccharides with mannose, glucose and galactose being the main monosaccharide components. Regarding the antioxidant activities, ORWP and ORAP showed effective 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity and lipid peroxidation inhibitory effects, as well as moderate reducing power and Fe2+ chelating activity. For the hepatoprotective activity, administration of ORWP and ORAP prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities in a carbon tetrachloride-induced acute liver damage model, suppressed hepatic malondialdehyde formation and stimulated the activities of hepatic superoxide dismutase and glutathione peroxidase. Thus, we speculate that ORWP and ORAP may protect the liver from CCl4-induced hepatic damage via antioxidant mechanisms.
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Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-l-arabinopyranoside (1

Changbai Mountain Ginseng (CMG, Panax ginseng C.A. Mey) is a traditional medicine commonly found in Northeast China and grows at elevations of 2000 m or higher in the Changbai Mountain Range. CMG, considered to be a “buried treasure medicine”, is priced higher than

Thiourea derivatives demonstrate potent cytotoxic activity against various leukemias and many tumor cell lines. In our previous study, the combination of thiourea and phosphonate has been proven as an effective strategy for developing antitumor agents. Herein, we synthesized and evaluated a series of

Thiourea derivatives demonstrate potent cytotoxic activity against various leukemias and many tumor cell lines. In our previous study, the combination of thiourea and phosphonate has been proven as an effective strategy for developing antitumor agents. Herein, we synthesized and evaluated a series of novel chiral dipeptide thioureas containing an α-aminophosphonate moiety as antitumor agents. Finally, we developed novel dipeptide thioureas 11d and 11f that showed comparable inhibition with that of Cisplatin against BGC-823 and A-549 cells, respectively.
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Many Helianthemum species (Cistaceae) are recognized for their various medicinal virtues. Helianthemum ruficomum is an endemic species to the septentrional Sahara on which no report is available so far. The purpose of this work was to investigate the chemical composition and the radical

Many Helianthemum species (Cistaceae) are recognized for their various medicinal virtues. Helianthemum ruficomum is an endemic species to the septentrional Sahara on which no report is available so far. The purpose of this work was to investigate the chemical composition and the radical scavenging capacity of this species and its isolated components. Collected from Mougheul (south-west of Algeria), the aerial parts were macerated with 80% EtOH/H2O, after evaporation, the remaining extract was diluted with H2O and extracted with petroleum ether, chloroform, ethyl acetate and n-butanol. EtOAc and n-BuOH extracts were evaluated for their free radical scavenging capacity by on-line HPLC-ABTS•+ assay. The obtained data which were confirmed by TEAC and ORAC assays, allowed guiding the fractionation of these extracts by CC, TLC and reverse phase HPLC. Among the components, 14 were isolated and identified by spectroscopic analyses: protocatechuic acid (1), trans-tiliroside (2), cis-tiliroside (3), astragalin (4), picein (7), vanillic acid 4-O-β-d-glucopyranoside (8), lavandoside (9), 4-hydroxybenzoic acid 4-O-β-d-glucopyranoside (10), nicotiflorin (11), rutin (12), vicenin-2 (13), narcissin (14) and stigmasterol (5) and β-sitosterol (6) as a mixture (71% and 29%, respectively). Compounds 5, 7, 8, 9, 10 and 14 were new for the genus Helianthemum. The antioxidant power of all the isolated compounds was also evaluated by HPLC-ABTS•+, TEAC and ORAC assays. The results clearly indicated high antioxidant potential of the extracts and tested compounds of this species especially, compounds 1, 4, 8, 9, 10 and 12.
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Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.
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Room-temperature ionic liquids (RTILs) are an emerging class of electrolytes for supercapacitors. In this work, we investigate the effects of different supercapacitor models and anion shape on the electrical double layers (EDLs) of two different RTILs: 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf2N]) and 1-ethyl-3-methylimidazolium

Room-temperature ionic liquids (RTILs) are an emerging class of electrolytes for supercapacitors. In this work, we investigate the effects of different supercapacitor models and anion shape on the electrical double layers (EDLs) of two different RTILs: 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf2N]) and 1-ethyl-3-methylimidazolium 2-(cyano)pyrrolide ([Emim][CNPyr]) by molecular dynamics (MD) simulation. The EDL microstructure is represented by number densities of cations and anions, and the potential drop near neutral and charged electrodes reveal that the supercapacitor model with a single electrode has the same EDL structure as the model with two opposite electrodes. Nevertheless, the employment of the one-electrode model without tuning the bulk density of RTILs is more time-saving in contrast to the two-electrode one. With the one-electrode model, our simulation demonstrated that the shapes of anions significantly imposed effects on the microstructure of EDLs. The EDL differential capacitance vs. potential (C-V) curves of [Emim][CNPyr] electrolyte exhibit higher differential capacitance at positive potentials. The modeling study provides microscopic insight into the EDLs structure of RTILs with different anion shapes.
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Neuroblastomas are the most common solid extracranial tumors in childhood. We investigated the anticancer effect of cearoin isolated from Dalbergia odorifera in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with various doses of cearoin. The viability was measured by MTT assay. DCFDA

Neuroblastomas are the most common solid extracranial tumors in childhood. We investigated the anticancer effect of cearoin isolated from Dalbergia odorifera in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with various doses of cearoin. The viability was measured by MTT assay. DCFDA fluorescence assay and Griess assay were used for the measurement of intracellular reactive oxygen species (ROS) and nitric oxide (NO), respectively. Western blot analysis was performed to clarify the molecular pathway involved. Cearoin induced cell death in a dose-dependent manner. Cearoin increased the phosporylation of ERK, the conversion of LC3B-I to LC3B-II, decrease in Bcl2 expression, the activation of caspase-3, and the cleavage of PARP, indicating the induction of autophagy and apoptosis. Furthermore, cearoin treatment increased the production of ROS and NO. Co-treatment with the antioxidant N-acetylcysteine completely abolished cearoin-mediated autophagy, ERK activation and apoptosis, suggesting the critical role of ROS in cearoin-induced anticancer effects. Moreover, co-treatment with ERK inhibitor PD98059 partially reversed cearoin-induced cell death, indicating the involvement of ERK in cearoin anticancer effects. These data reveal that cearoin induces autophagy, ERK activation and apoptosis in neuroblastoma SH-SY5Y cells, which is mediated primarily by ROS generation, suggesting its therapeutic application for the treatment of neuroblastomas.
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Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted compaction of GGBP and lead to the increase in ordering of its structure. Concentrated solutions of PEG-12000 and PEG-4000 caused GGBP aggregation. Although Ficoll-70 and Dextran-70 also promoted increase in the GGBP ordering, the structural outputs were different for different crowders. For example, in comparison with the GGBP in buffer, the intrinsic fluorescence spectrum of this protein was shifted to short-wave region in the presence of PEGs but was red-shifted in the presence of Ficoll-70 and Dextran-70. It was hypothesized that this difference could be due to the specific interaction of GGBP with the sugar-based polymers (Ficoll-70 and Dextran-70), indicating that protein can adopt different conformations in solutions containing molecular crowders of different chemical nature. It was also shown that all tested crowding agents were able to stabilize GGBP structure shifting the GGBP guanidine hydrochloride (GdnHCl)-induced unfolding curves to higher denaturant concentrations, but their stabilization capabilities did not depend on the hydrodynamic dimensions of the polymers molecules. Refolding of GGBP was complicated by protein aggregation in all tested solutions of crowding agents. The lowest yield of refolded protein was achieved in the highly concentrated solutions of PEG-12000. These data support the previous notion that the influence of macromolecular crowders on proteins is rather complex phenomenon that extends beyond the excluded volume effects.
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Quinine is an alkaloid with powerful antimalarial activity, isolated from the bark of Peru’s cinchona trees. Quinidine is an erythro diastereoisomer of quinine also exhibiting antimalarial activity. Conformational studies performed so far had never identified conformers with intramolecular hydrogen bonds (IHB). The current

Quinine is an alkaloid with powerful antimalarial activity, isolated from the bark of Peru’s cinchona trees. Quinidine is an erythro diastereoisomer of quinine also exhibiting antimalarial activity. Conformational studies performed so far had never identified conformers with intramolecular hydrogen bonds (IHB). The current study shows the possibility of conformers with an IHB between the quinuclidine and quinoline moieties of these molecules. The study was performed at different levels of theory: Hartree Fock (HF) with the 6-31G(d,p) basis set, Density Functional Theory (DFT) with the B3LYP functional and the 6-31+G(d,p) basis set and Møller–Plesset Perturbation Theory (MP2) with the 6-31+G(d,p) basis set, to confirm the results. The results suggest that the stabilising effect of this IHB is weaker or comparable with respect to the stabilising effect of the preferred mutual orientation of the two moieties. Although the IHB-containing conformers may not be the lowest energy ones, their relative energy is sufficiently low for them to be included among the possible ones responsible for the compounds’ antimalarial activity.
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Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery

Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407), poloxamer 188 (P188) and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel) and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG) was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.
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Bee bread (BB) is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives

Bee bread (BB) is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives located in different apiaries near Bragança, in the northeast region of Portugal, and one BB commercial sample were characterized by high-performance liquid chromatography coupled to a diode array detector and electrospray mass spectrometry (HPLC-DAD-ESI/MS) in terms of phenolic compounds, such as flavonoid glycoside derivatives. Furthermore, the samples were screened, using in vitro assays, against different human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HeLa (cervical carcinoma) and HepG2 (hepatocellular carcinoma), and also against non-tumor liver cells (porcine liver cells, PLP2). The main phenolic compounds found were flavonol derivatives, mainly quercetin, kaempferol, myricetin, isorhamnetin and herbacetrin glycoside derivatives. Thirty-two compounds were identified in the six BB samples, presenting BB1 and BB3 with the highest contents (6802 and 6480 µg/g extract, respectively) and the highest number of identified compounds. Two isorhamnetin glycoside derivatives, isrohamnetin-O-hexosyl-O-rutinoside and isorhamnetin-O-pentosyl-hexoside, were the most abundant compounds present in BB1; on the other hand, quercetin-3-O-rhamnoside was the most abundant flavonol in BB3. However, it was not possible to establish a correlation between the flavonoids and the observed low to moderate cytotoxicity (ranging from >400 to 68 µg/mL), in which HeLa and NCI-H460 cell lines were the most susceptible to the inhibition. To the authors’ knowledge, this is the first report characterizing glycosidic flavonoids in BB samples, contributing to the chemical knowledge of this less explored bee product.
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The complete chloroplast (cp) genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions

The complete chloroplast (cp) genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions (IRa and IRb), of 23,774 bp each, as well as large (LSC, 88,858 bp) and small (SSC, 18,672 bp) single-copy regions. A total of 129 genes were identified in the cp genome, 16 of which were duplicated within the IR regions. Relative to other plant cp genomes, the L. japonica cp genome had a unique rearrangement between trnI-CAU and trnN-GUU. In L. japonica cpDNA, rps19, rpl2, and rpl23 move to the LSC region, from the IR region. The ycf1 pesudogene in the IR region is lost, and only one copy locates in the SSC region. Comparative cp DNA sequence analyses of L. japonica with other cp genomes reveal that the gene order, and the gene and intron contents, are slightly different. The introns in ycf2 and rps18 genes are found for the first time. Four genes (clpP, petB, petD, and rpl16) lost introns. However, its genome structure, GC content, and codon usage were similar to those of typical angiosperm cp genomes. All preferred synonymous codons were found to use codons ending with A/T. The AT-rich sequences were less abundant in the coding regions than in the non-coding ones. A phylogenetic analysis based on 71 protein-coding genes supported the idea that L. japonica is a sister of the Araliaceae species. This study identified unique characteristics of the L. japonica cp genome that contribute to our understanding of the cpDNA evolution. It offers valuable information for the phylogenetic and specific barcoding of this medicinal plant.
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This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives,

This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci.
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Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized

Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized gold nanoparticles (Au-GSH-Dox) has higher cytotoxic effects than free doxorubicin for feline fibrosarcoma cell lines with high glycoprotein P activity (FFS1, FFS3). The aim of the present study was to assess the effectiveness of intratumoural injection of Au-GSH-Dox on the growth of tumours from the FFS1 and FFS3 cell lines on chick embryo chorioallantoic membrane. This model has been utilized both in human and veterinary medicine for preclinical oncological studies. The influence of intratumoural injections of Au-GSH-Dox, glutathione-stabilized gold nanoparticles and doxorubicin alone on the Ki-67 proliferation marker was also checked. We demonstrated that the volume ratio of tumours from the FFS1 and FFS3 cell lines was significantly (p < 0.01) decreased after a single intratumoural injection of Au-GSH-Dox, which confirms the positive results of in vitro studies and indicates that Au-GSH-Dox may be a potent new therapeutic agent for feline injection-site sarcomas.
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The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.
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Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to

Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs) in plasma. ROS-scavenging and lipid hydroperoxide (LPO) generation assays revealed that gallic acid, 3-O-methylgallic acid, (+)-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.
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The Me2Si-bridged ansa-Cp/amido half-metallocene, [Me2Si(η5-Me4C5)(NtBu)]TiCl2, termed a “constrained-geometry catalyst (CGC)”, is a representative homogeneous Ziegler catalyst. CGC derivatives with the [1,2]azasilinane framework, in which the amide alkyl substituent

The Me2Si-bridged ansa-Cp/amido half-metallocene, [Me2Si(η5-Me4C5)(NtBu)]TiCl2, termed a “constrained-geometry catalyst (CGC)”, is a representative homogeneous Ziegler catalyst. CGC derivatives with the [1,2]azasilinane framework, in which the amide alkyl substituent is joined by the Si-bridge, were prepared, and the catalytic performances of these species was studied. Me4C5HSi(Me)(CH2CH=CH2)-NH(C(R)(R’)CH=CH2) (R, R’ = H or methyl; Me4C5H = tetramethylcyclopentadienyl) was susceptible to ring closure metathesis (RCM) when treated with Schrock’s Mo-catalyst to afford -Si(Me4C5H)(Me)CH2CH=CHC(R)(R’)NH- containing a six-membered ring framework. Using the precursors and the products of RCM, various CGC derivatives, i.e., [-Si(η5-Me4C5)(Me)CH2CH=CHC(R)(H)N-]TiMe2 (13, R = H; 15, R = Me), [-Si(η5-Me4C5)(Me)CH2CH2CH2CH2N]TiMe2 (14), [(η5-Me4C5)Si(Me)(CH2CH=CH2)NCH2CH=CH2]TiMe2 (16), [(η5-Me4C5)Si (Me)(CH=CH2)NCH2CH=CH2]TiMe2 (17), and [(η5-Me4C5)Si(Me)(CH2CH3)NCH2CH2CH3]TiMe2 (18), were prepared. The catalytic activity of the newly prepared complexes was lower than that of CGC when activated with [Ph3C][B(C6F5)4]/iBu3Al. However, the catalytic activity of these species was improved by using tetrabutylaluminoxane ([iBu2Al]2O) instead of iBu3Al and the activity of 14/[Ph3C][B(C6F5)4]/[iBu2Al]2O was comparable to that of CGC/[Ph3C][B(C6F5)4]/iBu3Al (4.7 and 5.0 × 106 g/mol-Ti, respectively). Advantageously, the newly prepared complexes produced higher molecular weight poly(ethylene-co-1-octene)s than CGC.
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Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50

Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50: 11.6 μM (1), and 12.4 μM (3)] and HeLa [IC50: 22.4 μM (1) and 19.4μM (3)] cell lines is reported. Their antioxidant potential was evaluated by spectrophotometric method, using DPPH radical or Fe (TPTZ)3+ complex, and EPR spectroscopy, therefore the compounds 1 and 3 showed remarkable antioxidant activity simultaneously with a cytotoxic effect on A2780 and HeLa cell lines. Furthermore, based on theoretical quantum chemical calculation, the present study analyzed the chemoselectivity of the hydrogen extraction from the indolyl-hydrazinil-thiazoles in reaction with free radicals.
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Six new furan derivatives, named 5-(3-methoxy-3-oxopropyl)-furan-2-carboxylic acid (1), 1-(5-(2-hydroxypropanoyl)-furan-2-yl)-pentan-3-one (2), 2-hydroxy-1-(5-(1-hydroxypentyl)-furan-2-yl)-propan-1-one (3), 1-(5-(1,2-dihydroxypropyl)-furan-2-yl)-pentan-1-one (4), 5-(1-hydroxypent-4-en-1-yl)-furan-2-carboxylic acid (5) and 5-(3-hydroxypentyl)-furan-2-carboxylic acid (6), together with two new natural products, named 5-(1-hydroxypentyl)-furan-2-carboxylic acid (7) and (E)-5-(2-carboxyvinyl)-furan-2-carboxylic acid (8), were isolated from the solid rice fermentation of endophytic fungus Coriolopsis sp. J5, which was derived from mangrove plant Ceriops tagal. Their structures were unambiguously elucidated based on 1D and 2D NMR spectroscopy, and by HRESIMS measurements, as well as by comparison with the literature.
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We report the effect of weak base addition to acidic polymer hole-collecting layers in normal-type polymer:fullerene solar cells. Varying amounts of the weak base aniline (AN) were added to solutions of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The acidity of the aniline-added PEDOT:PSS solutions gradually decreased from

We report the effect of weak base addition to acidic polymer hole-collecting layers in normal-type polymer:fullerene solar cells. Varying amounts of the weak base aniline (AN) were added to solutions of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The acidity of the aniline-added PEDOT:PSS solutions gradually decreased from pH = 1.74 (AN = 0 mol% ) to pH = 4.24 (AN = 1.8 mol %). The electrical conductivity of the PEDOT:PSS-AN films did not change much with the pH value, while the ratio of conductivity between out-of-plane and in-plane directions was dependent on the pH of solutions. The highest power conversion efficiency (PCE) was obtained at pH = 2.52, even though all devices with the PEDOT:PSS-AN layers exhibited better PCE than those with the pristine PEDOT:PSS layers. Atomic force microscopy investigation revealed that the size of PEDOT:PSS domains became smaller as the pH increased. The stability test for 100 h illumination under one sun condition disclosed that the PCE decay was relatively slower for the devices with the PEDOT:PSS-AN layers than for those with pristine PEDOT:PSS layers.
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This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint), Mentha spicata L.

This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint), Mentha spicata L. subsp. crispata (spearmint), and Mentha suaveolens Ehrh. (pineapple mint). Qualitative and quantitative analysis of the essential oils isolated from the selected Mentha species was performed by gas chromatography coupled with mass spectrometry (GC-MS). The anti-inflammatory activity of the essential oils was determined by the rat paw edema test induced by λ-carrageenan. The antinociceptive effect of the essential oils was evaluated by the writhing test in mice, using 1% (v/v) acetic acid solution administered intraperitonealy and by the hot plate test in mice. The results showed a menthol chemotype for M. piperita pallescens, a carvone chemotype for M. spicata, and a piperitenone oxide chemotype for M. suaveolens. The essential oil from M. spicata L. (EOMSP) produced statistically significant and dose-dependent anti-inflammatory and antinociceptive effects.
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Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network

Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network in primary prostate cancer specimens and in metastatic tumors. Betulinic acid (BA), is a triterpenoid that has been reported to be an effective inducer of apoptosis through modification of several signaling pathways. Our objective was to investigate the pathways involved in BA-induced apoptosis in human prostate cancer cells. We employed the androgen-responsive LNCaP cells harboring wild-type p53, and androgen-refractory DU145 cells possessing mutated p53 with high constitutive NF-κB activity. Inhibition of cell survival by BA at 10 and 20 µM concentrations occurred as a result of alteration in Bax/Bcl-2 ratio in both cell lines that led to an increased cytochrome C release, caspase activation and poly(ADP)ribose polymerase (PARP) cleavage, leading to apoptosis. BA treatment resulted in stabilization of p53 through increase in phosphorylation at Ser15 in LNCaP cells, but not in DU145 cells, and induction of cyclin kinase inhibitor p21/Waf1 in both cell types. Furthermore, treatment of both prostate cancer cells with BA decreased the phosphorylation of IκB kinase (IKK)α and I-kappa-B-alpha (IκBα) inhibiting the nuclear location of NF-κB/p65 causing cytosolic accumulation and resulting in its decreased nuclear binding. We demonstrate that BA may induce apoptosis by stabilizing p53 and downregulating NF-κB pathway in human prostate cancer cells, irrespective of the androgen association, and therefore can potentially be developed as a molecule of interest in cancer chemoprevention.
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Anthraquinone (9,10-anthraquinone) and several hydroxy derivatives, including purpurin (1,2,4-trihydroxyanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), and chrysazin (1,8-dihydroxyanthraquinone), were evaluated for antioxidative and anti-inflammatory activities in chemical assays and mammalian cells (murine macrophage RAW 264.7 cells). Several tests were used to assess their activities: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free

Anthraquinone (9,10-anthraquinone) and several hydroxy derivatives, including purpurin (1,2,4-trihydroxyanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), and chrysazin (1,8-dihydroxyanthraquinone), were evaluated for antioxidative and anti-inflammatory activities in chemical assays and mammalian cells (murine macrophage RAW 264.7 cells). Several tests were used to assess their activities: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical; ABTS radical cation; hydrogen peroxide scavenging; reduction of potassium ferricyanide; chelation of ferrous ions; inhibition of lipid peroxidation; inhibition of nitric oxide generation; scavenging of the intracellular hydroxyl radical; expression of NLRP3 polypeptide for inflammasome assembly; and quantitation of proinflammatory cytokine interleukin 1β (IL-1β) for inflammasome activation. The results show that purpurin, from the root of the madder plant (Rubia tinctorum L.), exhibited the highest antioxidative activity in both chemical and cultured cell antioxidant assays. The antioxidative activities of the other three anthraquinones were lower than that of purpurin. In addition, purpurin could down-regulate NLRP3 inflammasome assembly and activation, suggesting that it might protect foods against oxidative damage and prevent in vivo oxidative stress and inflammation. Structure-activity relationships and the significance of the results for food quality and human health are discussed.
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In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and

In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and pyrazolylthioamide to give 1,3-thiazoles derivatives. Subsequently, 3-phenyl2-en-1-one was used to synthesize substituted pyridines and substituted nicotinic acid ester. The latter was converted to its azide compound which was reacted with aromatic amines and phenol to give substituted urea and phenylcarbamate containing 1,2,3-triazole moiety. The newly synthesized compounds were established by elemental analysis, spectral data and alternative synthesis whenever possible.
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The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has been developed and applied for biomass bioconversion. The crosslinked aggregates could purify and immobilize enzymes in a single operation, and could then be combined with magnetic nanoparticles (MNPs), which provides easy separation of the materials. The immobilized cellulase showed a better activity at a wider temperature range and pH values than that of the free cellulase. After six cycles of consecutive reuse, the immobilized cellulase performed successful magnetic separation and retained 74% of its initial activity when carboxylmethyl cellulose (CMC) was used as the model substrate. Furthermore, the structure and morphology of the immobilized cellulase were studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the immobilized cellulase was shown to hydrolyze bamboo biomass with a yield of 21%, and was re-used in biomass conversion up to four cycles with 38% activity retention, which indicated that the immobilized enzyme has good potential for biomass applications.
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Response surface methodology (RSM), based on a central composite design, was used to determine the best liquid-to-raw material ratio (10:3–15 mL/g), extraction time (1–3 h), and ethanol concentration (50%–100%) for maximum content of α-asarone from Perilla frutescens (PF) extract. Experimental values of α-asarone

Response surface methodology (RSM), based on a central composite design, was used to determine the best liquid-to-raw material ratio (10:3–15 mL/g), extraction time (1–3 h), and ethanol concentration (50%–100%) for maximum content of α-asarone from Perilla frutescens (PF) extract. Experimental values of α-asarone were 9.51–46.36 mg/g; the results fitted a second-order quadratic polynomial model and correlated with the proposed model (R2 > 0.9354). The best conditions were obtained with extraction time of 1.76 h, liquid-to-raw material ratio of 10:13.5 mL/g, and ethanol concentration of 90.37%. Under these conditions, the model predicted extraction content of 40.56 mg/g, while experimental PF content of α-asarone was 43.84 mg/g dried plant. Optimized conditions determined for maximum content of α-asarone were similar to the experimental range. Experimental values agreed with those predicted, thus validating and indicating suitability of both the model and the RSM approach for optimizing extraction conditions. In addition, a reliable, reproducible and accurate method for the quantitative determination of α-asarone by High Performance Liquid Chromatography (HPLC) analysis was developed with limit of detection (LOD), limit of quantitation (LOQ) values of 0.10 and 0.29 µg/mL and excellent linearity (R2 > 0.9999).
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Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo-LPI, and the hypoglycemic

Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo-LPI, and the hypoglycemic and antioxidant effects on alloxan-induced diabetic mice were assessed. Mo-LPI was obtained by aqueous extraction, ammonium sulphate precipitation and dialysis.The electrophoresis profile and proteolytic hydrolysis confirmed its protein nature. Mo-LPI showed hemagglutinating activity, cross-reaction with anti-insulin antibodies and precipitation after zinc addition. Single-dose intraperitoneal (i.p.) administration of Mo-LPI(500 mg/kg·bw) reduced the blood glucose level (reductions of 34.3%, 60.9% and 66.4% after 1, 3 and 5 h, respectively). The effect of Mo-LPI was also evidenced in the repeated dose test with a 56.2% reduction in the blood glucose level on the 7th day after i.p. administration. Mo-LPI did not stimulate insulin secretion in diabetic mice. Mo-LPI was also effective in reducing the oxidative stress in diabetic mice by a decrease in malondialdehyde level and increase in catalase activity. Mo-LPI (2500 mg/kg·bw) did not cause acute toxicity to mice. Mo-LPI is a promising alternative or complementary agent to treat diabetes.
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Plant tryptophan decarboxylase (TDC) converts tryptophan into tryptamine, precursor of indolealkylamine alkaloids. The recent finding of tryptamine metabolites in Citrus plants leads to hypothesize the existence of TDC activity in this genus. Here, we report for the first time that, in Citrus x

Plant tryptophan decarboxylase (TDC) converts tryptophan into tryptamine, precursor of indolealkylamine alkaloids. The recent finding of tryptamine metabolites in Citrus plants leads to hypothesize the existence of TDC activity in this genus. Here, we report for the first time that, in Citrus x limon seedlings, deuterium labeled tryptophan is decarboxylated into tryptamine, from which successively deuterated N,N,N-trimethyltryptamine is formed. These results give an evidence of the occurrence of the TDC activity and the successive methylation pathway of the tryptamine produced from the tryptophan decarboxylation. In addition, with the aim to identify the genetic basis for the presence of TDC, we carried out a sequence similarity search for TDC in the Citrus genomes using as a probe the TDC sequence reported for the plant Catharanthus roseus. We analyzed the genomes of both Citrus clementina and Citrus sinensis, available in public database, and identified putative protein sequences of aromatic l-amino acid decarboxylase. Similarly, 42 aromatic l-amino acid decarboxylase sequences from 23 plant species were extracted from public databases. Potential sequence signatures for functional TDC were then identified. With this research, we propose for the first time a putative protein sequence for TDC in the genus Citrus.
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In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10−5 M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated.
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In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry

In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular docking and dynamics study. DSC and PXRD results indicated that PPD crystallinity in SDs was significantly reduced, and that the majority of PPD is amorphous. No interaction was observed between PPD and polymers on FTIR and NMR spectra. Molecular docking and dynamic calculations indicated that the PPD molecule localized to the interpolated charged surface, rather than within the amorphous polymer chain network, which might help prevent PPD crystallization, consequently enhancing the PPD dispersion in polymers. An in vitro dissolution study revealed that the SDs considerably improved the PPD dissolution performance in distilled water containing 0.35% Tween-80 (T-80). Furthermore, among three PPD-SDs formulations, Poloxamer188 (F68) was the most effective in improving the PPD solubility and was even superior to the mixed polymers. Therefore, the SD prepared with F68 as a hydrophilic polymer carrier might be a promising strategy for improving solubility and in vitro dissolution performance. F68-based SD, containing PPD with a melting-solvent preparation method, can be used as a promising, nontoxic, quick-release, and effective intermediate for other pharmaceutical formulations, in order to achieve a more effective drug delivery.
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The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter

The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry.
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Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer

Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP) inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells.
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The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.
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The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30;

The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; CSD3) at the weight ratio of 1:1 (drug:polymer) using a spray-drying method. The prepared CSDs were characterized by aqueous solubility, differential scanning calorimetry (DSC), powder X-ray diffraction (p-XRD), scanning electron microscopy (SEM), aqueous viscosity, and dissolution test in various media. The oral bioavailability of CSDs was also evaluated in rats and compared with cefdinir powder suspension. The cefdinir in CSDs was amorphous form, as confirmed in the DSC and p-XRD measurements. The developed CSDs commonly resulted in about 9.0-fold higher solubility of cefdinir and a significantly improved dissolution profile in water and at pH 1.2, compared with cefdinir crystalline powder. Importantly, the in vivo oral absorption (represented as AUCinf) was markedly increased by 4.30-, 6.77- and 3.01-fold for CSD1, CSD2, and CSD3, respectively, compared with cefdinir suspension in rats. The CSD2 prepared with CMC-Na would provide a promising vehicle to enhance dissolution and bioavailability of cefdinir in vivo.
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In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in

In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in duodenum or jejunum. Also, Compound 1 possess two ionic species, first above of pH 4.43 and, the second one is present over pH 6.08. The apparent permeability in everted sac rat intestine model was 8.73 × 10−6 cm/s in duodenum and 1.62 × 10−5 cm/s in jejunum, suggesting that Compound 1 has low permeability. Elimination constant after an oral administration of 50 μg/kg in Wistar rat was 1.81 h−1, absorption constant was 3.05 h−1, Cmax was 3.57 μg/mL at 0.33 h, AUC0–α was 956.54 μ/mL·h and distribution volume was 419.4 mL. To IV administration at the same dose, ke was 1.21 h−1, Vd was 399.6 mL and AUC0–α was 747.81 μ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound 1 is metabolized to Compound 2 probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound 1 would be considered as a prodrug of Compound 2 with potential as an antidiabetic and anti dyslipidemic agent.
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Anthocyanins are important compounds for red grape and red wine quality, and can be influenced by supply of nutrients such as nitrogen, phosphorus, potassium, zinc, and iron. The present work aims to gain a better understanding of the effect of iron supply on

Anthocyanins are important compounds for red grape and red wine quality, and can be influenced by supply of nutrients such as nitrogen, phosphorus, potassium, zinc, and iron. The present work aims to gain a better understanding of the effect of iron supply on anthocyanins concentration in grape berries. To this end, own-rooted four-year-old Cabernet Sauvignon grapevines (Vitis vinifera) were fertigated every three days with 0, 23, 46, 92, and 184 μM iron (Fe) from ferric ethylenediamine di (o-hydroxyphenylacetic) acid (Fe-EDDHA) in a complete nutrient solution. Fe deficiency or excess generally led to higher concentrations of titratable acidity and skin/berry ratio, and to lower reducing sugar content, sugar/acid ratio, pH, berry weight, and concentration of anthocyanins. Most of the individual anthocyanins detected in this study, except cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and cyanidin-3-O-(6-O-coumaryl)-glucoside, in moderate Fe treatment (46 μM) grapes were significantly higher than those of other treatments. Genes encoding chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), leucoanthocyanidin dioxygenase (LDOX), and anthocyanin O-methyltransferase (AOMT) exhibited higher transcript levels in berries from plants cultivated with 46 μM Fe compared to the ones cultivated with other Fe concentrations. We suggest that grape sugar content, anthocyanins content, and transcriptions of genes involved in anthocyanin biosynthesis were correlated with Fe supply concentrations.
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The use of ketohexose isomerases is a powerful tool in lactose whey processing, but these enzymes can be very sensitive and expensive. Development of immobilized/stabilized biocatalysts could be a further option to improve the process. In this work, β-galactosidase from Bacillus circulans,

The use of ketohexose isomerases is a powerful tool in lactose whey processing, but these enzymes can be very sensitive and expensive. Development of immobilized/stabilized biocatalysts could be a further option to improve the process. In this work, β-galactosidase from Bacillus circulans, l-arabinose (d-galactose) isomerase from Enterococcus faecium, and d-xylose (d-glucose) isomerase from Streptomyces rubiginosus were immobilized individually onto Eupergit C and Eupergit C 250 L. Immobilized activity yields were over 90% in all cases. With the purpose of increasing thermostability of derivatives, two post-immobilization treatments were performed: alkaline incubation to favor the formation of additional covalent linkages, and blocking of excess oxirane groups by reacting with glycine. The greatest thermostability was achieved when alkaline incubation was carried out for 24 h, producing l-arabinose isomerase-Eupergit C derivatives with a half-life of 379 h and d-xylose isomerase-Eupergit C derivatives with a half-life of 554 h at 50 °C. Preliminary assays using immobilized and stabilized biocatalysts sequentially to biotransform lactose at pH 7.0 and 50 °C demonstrated improved performances as compared with soluble enzymes. Further improvements in ketohexose productivities were achieved when the three single-immobilizates were incubated simultaneously with lactose in a mono-reactor system.
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Agricultural waste cow dung was used as feedstock for the production of a high value–added chemical levulinic acid (LA) in dilute acid aqueous solutions. A high LA yield of 338.9 g/kg was obtained from the pretreated cow dung, which was much higher than

Agricultural waste cow dung was used as feedstock for the production of a high value–added chemical levulinic acid (LA) in dilute acid aqueous solutions. A high LA yield of 338.9 g/kg was obtained from the pretreated cow dung, which was much higher than that obtained from the crude cow dung (135 g/kg), mainly attributed to the breakage of the lignin fraction in the lignocellulose structure of the cow dung by potassium hydroxide (KOH) pretreatment, and thus enhanced the accessibility of cow dung to the acid sites in the catalytic reaction. Meanwhile, another value-added chemical formic acid could be obtained with a yield of ca. 160 g/kg in the process, implying a total production of ca. 500 g/kg yield for LA and formic acid from the pretreated cow dung with the proposed process. The developed process was shown to be tolerant to high initial substrate loading with a satisfied LA yield. This work provides a promising strategy for the value-increment utilization of liglocellulosic agricultural residues.
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Rhizome of Ligusticum chuanxiong is an effective medical plant, which has been extensively applied for centuries in migraine and cardiovascular diseases treatment in China. Polysaccharides from this plant have been shown to have interesting bioactivities, but previous studies have only been performed on

Rhizome of Ligusticum chuanxiong is an effective medical plant, which has been extensively applied for centuries in migraine and cardiovascular diseases treatment in China. Polysaccharides from this plant have been shown to have interesting bioactivities, but previous studies have only been performed on the neutral polysaccharides. In this study, LCP-I-I, a pectic polysaccharide fraction, was obtained from the 100 °C water extracts of L. chuangxiong rhizomes and purified by diethylaminethyl (DEAE) sepharose anion exchange chromatography and gel filtration. Monosaccharide analysis and linkage determination in addition to Fourier transform infrared (FT-IR) spectrometer and Nuclear magnetic resonance (NMR) spectrum, indicated that LCP-I-I is a typical pectic polysaccharide, with homo-galacturonan and rhamnogalacturonan type I regions and arabinogalactan type I and type II (AG-I/AG-II) side chains. LCP-I-I exhibited potent complement fixation activity, ICH50 of 26.3 ± 2.2 µg/mL, and thus has potential as a natural immunomodulator.
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In the present study, photoirradiation molecularly imprinted polymer (MIP) with azobenzene was used as a functional monomer for the selective separation of the branched cyclodextrins. The functional monomer 4-methacryloyloxy azobenzene (MAA) and the molecular template 6-O-α-d-maltosyl-β-cyclodextrin (G2-β-CD) were implemented

In the present study, photoirradiation molecularly imprinted polymer (MIP) with azobenzene was used as a functional monomer for the selective separation of the branched cyclodextrins. The functional monomer 4-methacryloyloxy azobenzene (MAA) and the molecular template 6-O-α-d-maltosyl-β-cyclodextrin (G2-β-CD) were implemented for the molecular imprinting. The core-shell structure of photoirradiation MIP was visualized by the transmission electron microscopy (TEM). With Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA), we identified that G2-β-CD was imprinted into the polymer and removed from the MIP. The binding association constant (Ka) and the maximum number of the binding site (Nmax) were 1.72 × 104 M−1 and 7.93 μmol·g−1 MIP, respectively. With alternate irradiation at 365 and 440 nm light, the prepared MIP reversibly released and rebound to the G2-β-CD, which resulted in the nearly zero amount of G2-β-CD in the solution. The HPLC results indicated that the purity of G2-β-CD could reach 90.8% after going through MIP. The main finding of our study was that the photoirradiation of MIP was an easy and effective method for the selective separation of the branched cyclodextrins.
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Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of 1, 4, and 5, four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene (3), herniarin (6), scoparone (7), and 4′,7-dimethylapigenin (8). In addition, the structure of calein C (5) was confirmed by X-ray analysis. Pharmacological evaluation of the essential oil of the species (31.6–316.2 mg/kg, p.o.) provoked also an important decrement of blood glucose levels during an OSTT. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and active essential oil obtained by hydrodistillation revealed that chromene 1 was the major component (19.92%); sesquiterpenes represented the highest percentage of the essential oil content (55.67%) and included curcumene (7.10%), spathulenol (12.95%) and caryophyllene oxide (13.0%). A suitable High Performance Liquid Chromatography (HPLC) method for quantifying chromenes 1 and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2) was developed and validated according to standard protocols.
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Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE),

Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy

Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy to prepare H. cordata essential oil (HEO) safely and effectively by combining the solvent extraction and the macroporous resin purification flexibly, and then encapsulating it using microemulsion. The extraction and purification process were optimized by orthogonal experimental design and adsorption-desorption tests, respectively. The average houttuynin content in pure HEO was then validated at 44.3% ± 2.01%, which presented a great potential for industrial application. Subsequently, pure HEO-loaded microemulsion was prepared by high-pressure homogenization and was then fully characterized. Results showed that the pure HEO-loaded microemulsion was successfully prepared with an average particle size of 179.1 nm and a high encapsulation rate of 94.7%. Furthermore, safety evaluation tests and in vitro antiviral testing indicated that the safety and activity of HEO were significantly improved after purification using D101 resin and were further improved by microemulsion encapsulation. These results demonstrated that the purification of HEO by macroporous resin followed by microemulsion encapsulation would be a promising approach for industrial application of HEO for the antiviral therapies.
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The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior

The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in polymers has been measured and modeled during the last years, the APS phenomenon is still poorly understood. In this study, the crystallization behavior, APS, and glass-transition temperatures formulations of ibuprofen and felodipine in polymeric PLGA excipients exhibiting different ratios of lactic acid and glycolic acid monomers in the PLGA chain were investigated by means of hot-stage microscopy and DSC. APS and recrystallization was observed in ibuprofen/PLGA formulations, while only recrystallization occurred in felodipine/PLGA formulations. Based on a successful modeling of the crystallization behavior using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), the occurrence of APS was predicted in agreement with experimental findings.
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α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,β-amyrins, obtained as major compounds from the same oleoresins. Using a

α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,β-amyrins, obtained as major compounds from the same oleoresins. Using a very simple, high yield procedure, and using a readily commercially available mixture of α,β-amyrins as substrate, the binary compound α,β-amyrenone was synthesized and submitted to physico-chemical characterization using different techniques such as high-performance liquid chromatography, nuclear magnetic resonance (1H and 13C), mass spectrometry, scanning electron microscopy, differential scanning calorimetry, thermogravimetry and derivative thermogravimetry, and Fourier transform infrared spectroscopy (FTIR). Biological effects were also evaluated by studying the inhibition of enzymes involved in the carbohydrate and lipid absorption process, such as α-amylase, α-glucosidase, lipase, and their inhibitory concentration values of 50% of activity (IC50) were also determined. α,β-Amyrenone significantly inhibited α-glucosidase (96.5% ± 0.52%) at a concentration of 1.6 g/mL. α,β-Amyrenone, at a concentration of 100 µg/mL, showed an inhibition rate on lipase with an IC50 value of 82.99% ± 1.51%. The substances have thus shown in vitro inhibitory effects on the enzymes lipase, α-glucosidase, and α-amylase. These findings demonstrate the potential of α,β-amyrenone for the development of drugs in the treatment of chronic metabolic diseases.
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In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1)

In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines. Among these compounds, 4-(3-propynylthio)-7-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline shows significant antiprolierative activity against T47D cells with IC50 values of 0.07 µM. In addition, 2-(3-Propynylthio)-6-[N-methyl-N-(3-propynyl)sulfa-moyl]quinoline and 2-(3-propynylseleno)-6-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC50 values of 0.09 and 0.50 µM, respectively. Furthermore, most of the tested compounds show a weak cytotoxic effect against the normal HFF-1 cell line. Additionally, in order to suggest a mechanism of action for their activity, all compounds are docked into the binding site of two human cytochrome P450 (CYP) isoenzymes. These data indicate that some of the title compounds display significant cytotoxic activity, possibly targeting the CYPs pathways.
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In this paper, a green microwave-assisted combustion approach to synthesize ZnO-NPs using zinc nitrate and Citrullus colocynthis (L.) Schrad (fruit, seed and pulp) extracts as bio-fuels is reported. The structure, optical, and colloidal properties of the synthesized ZnO-NP samples were studied. Results illustrate

In this paper, a green microwave-assisted combustion approach to synthesize ZnO-NPs using zinc nitrate and Citrullus colocynthis (L.) Schrad (fruit, seed and pulp) extracts as bio-fuels is reported. The structure, optical, and colloidal properties of the synthesized ZnO-NP samples were studied. Results illustrate that the morphology and particle size of the ZnO samples are different and depend on the bio-fuel. The XRD results revealed that hexagonal wurtzite ZnO-NPs with mean particle size of 27–85 nm were produced by different bio-fuels. The optical band gap was increased from 3.25 to 3.40 eV with the decreasing of particle size. FTIR results showed some differences in the surface structures of the as-synthesized ZnO-NP samples. This led to differences in the zeta potential, hydrodynamic size, and more significantly, antioxidant activity through scavenging of 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals. In in vitro cytotoxicity studies on 3T3 cells, a dose dependent toxicity with non-toxic effect of concentration below 0.26 mg/mL was shown for ZnO-NP samples. Furthermore, the as-synthesized ZnO-NPs inhibited the growth of medically significant pathogenic gram-positive (Bacillus subtilis and Methicillin-resistant Staphylococcus aurous) and gram-negative (Peseudomonas aeruginosa and Escherichia coli) bacteria. This study provides a simple, green and efficient approach to produce ZnO nanoparticles for various applications.
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New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III) porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the

New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III) porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus were evaluated after their incorporation into polyvinylpyrrolidone (PVP) micelles. The obtained results show that the PVP-formulations of the lapachones 4b–g and of the sulfonyl-lapachones 7e and 7g reduced the growth of S. aureus.
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Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole

Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole derivatives of dihydroartemisinin were synthesized in a single step. All these newly synthesized compounds were characterized and evaluated for their anti-HIV (Human Immunodeficiency Virus) potential in MT-4 cells. Interestingly; three of the synthesized triazole derivatives of dihydroartemisinin showed activities with half maximal inhibitory concentration (IC50) values ranging from 1.34 to 2.65 µM.
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The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and

The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and EA fraction guided fractionation by reverse-phase chromatography. The vasorelaxant effects of MET, fractions, sub-fractions and constituents were assessed on rat aorta pre-contracted with phenylephrine. Antioxidant activity was evaluated by using a DPPH assay. The results show that MET-induced vasodilation was dependent on NO/cGMP; and that the PI3K/Akt pathway seems to be the main route involved in eNOS activation. The EA fraction showed greater vasodilatory and antioxidant potency and was submitted to further fractionation. This allowed the isolation and characterization of quercetin, quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside and 1,4,6-tri-O-galloyl-β-d-glucose. Also, galloyl-HHDP-hexoside and myricetin deoxyhexoside were identified by HPLC-UV-MS. These compounds are being described for the first time for T. guianensis. 1,4,6-tri-O-galloyl-β-d-glucose and quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside showed no vasodilatory activity. Quercetin and myricetin glycoside seems to contribute to the MET activity, since they have been reported as vasodilatory flavonoids. MET-induced vasodilation could contribute to the hypotensive effect of T. guianensis previously reported.
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A series of Zn-modified NaY zeolites were prepared by the liquid-phase ion-exchange method with different Zn sources, including Zn(NO3)2, Zn(Ac)2 and ZnSO4. The samples were tested as adsorbents for removing an organic sulfur compound from a

A series of Zn-modified NaY zeolites were prepared by the liquid-phase ion-exchange method with different Zn sources, including Zn(NO3)2, Zn(Ac)2 and ZnSO4. The samples were tested as adsorbents for removing an organic sulfur compound from a model gasoline fuel containing 1000 ppmw sulfur. Zn(Ac)2-Y exhibited the best performance for the desulfurization of gasoline at ambient conditions. Combined with the adsorbents’ characterization results, the higher adsorption capacity of Zn(Ac)2-Y is associated with a higher ion-exchange degree. Further, the results demonstrated that the addition of 5 wt % toluene or 1-hexene to the diluted thiophene (TP) solution in cyclohexane caused a large decrease in the removal of TP from the model gasoline fuel. This provides evidence about the competition through the π-complexation between TP and toluene for adsorption on the active sites. The acid-catalyzed alkylation by 1-hexene of TP and the generated complex mixture of bulky alkylthiophenes would adsorb on the surface active sites of the adsorbent and block the pores. The regenerated Zn(Ac)2-Y adsorbent afforded 84.42% and 66.10% of the initial adsorption capacity after the first two regeneration cycles.
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The fruit of Melastoma sanguineum Sims is an edible and sweet wild fruit. In our previous study, the fruit was found to have a strong antioxidant property. In this study, an ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the

The fruit of Melastoma sanguineum Sims is an edible and sweet wild fruit. In our previous study, the fruit was found to have a strong antioxidant property. In this study, an ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the fruit of Melastoma sanguineum Sims, and a response surface methodology was used to optimize the conditions of UAE to maximize the extraction efficiency. The influence of five independent extraction parameters (ethanol concentration, solvent/material ratio, extracting time, temperature, and ultrasound power) on the extraction efficiency were investigated using a single factor experiment, and then a central composite rotatable design was used to investigate the interaction of three key parameters. The results showed that the optimal extraction conditions were 42.98% ethanol, 28.29 mL/g solvent/material ratio, 34.29 min extracting time, 60 °C temperature, and 600 W ultrasound power. Under these conditions, the Trolox equivalent antioxidant capacity (TEAC) value of the extracts was 1074.61 ± 32.56 μmol Trolox/g dry weight (DW). Compared with conventional maceration (723.27 ± 11.61 μmol Trolox/g DW) and Soxhlet extraction methods (518.37 ± 23.23 μmol Trolox/g DW), the UAE method improved the extraction efficiency, in a shorter period of time. In addition, epicatechin gallate, epicatechin, rutin, epigallocatechin, protocatechuic acid, chlorogenic acid, and quercetin, were identified and quantified in the fruit extracts of Melastoma sanguineum Sims by UPLC-MS/MS.
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Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular

Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular growth. In this study, in silico molecular protein-ligand docking protocols were performed with AutoDock Vina in order to evaluate the interaction of 800 natural compounds (NPs) from the NatProd Collection (http://www.msdiscovery.com/natprod.html), with four human HER family members: HER1 (PDB: 2ITW), HER2 (PDB: 3PP0), HER3 (PDB: 3LMG) and HER4 (PDB: 2R4B). The best binding affinity values (kcal/mol) for docking pairs were obtained for HER1-podototarin (−10.7), HER2-hecogenin acetate (−11.2), HER3-hesperidin (−11.5) and HER4-theaflavin (−10.7). The reliability of the theoretical calculations was evaluated employing published data on HER inhibition correlated with in silico binding calculations. IC50 values followed a significant linear relationship with the theoretical binding Affinity data for HER1 (R = 0.656, p < 0.0001) and HER2 (R = 0.543, p < 0.0001), but not for HER4 (R = 0.364, p > 0.05). In short, this methodology allowed the identification of several NPs as HER inhibitors, being useful in the discovery and design of more potent and selective anticancer drugs.
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Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins

Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14β)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC50 = 1.8 μM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480).
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Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC50 values against three cancer cell lines

Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC50 values against three cancer cell lines (A549, PC-3 and MCF-7). Most of the target compounds exhibited moderate cytotoxicity against the three cancer cell lines. Two selected compounds 14b, 14c were further tested for their activity against PI3Kα kinase, and the results indicated that compound 14c showed inhibitory activity against PI3Kα kinase with an IC50 value of 1.25 μM. Structure-activity relationships (SARs) and pharmacological results indicated that the replacement of the thiopyranopyrimidine with an imidazopyrazine was beneficial for the activity and the position of aryl group has a significant influence to the activity of these compounds. The compounds 13a–g in which an aryl group substituted at the C-4 position of the pyridine ring were more active than 12a–g substituted at the C-5 position. Moreover, the cytotoxicity of compounds 14a–g bearing phenylpyrimidine-carboxamides was better than that of the compounds 12a–g, 13a–g bearing phenylpyridine-carboxamides. Furthermore, the substituents on the benzene ring also had a significant impact on the cytotoxicity and the pharmacological results showed that electron donating groups were beneficial to the cytotoxicity.
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